Post-transplant renal failure

Background

• Common complication of renal transplant
• May be broadly classified as:
  • Acute allograft dysfunction, with increase in serum creatinine, failure of creatinine to decrease after transplantation, or proteinuria within about 1 to 3 months
  • Chronic allograft dysfunction, with slowly worsening renal function
  • Delayed graft function, where dialysis is required within the first week of transplantation
• May also be classified as:
  • Immediate or hyperacute (<1 week post-transplant)
  • Early (within 6 months post-transplant)
  • Late (6 or more months post-transplant)

Differential Diagnosis

Immediate Dysfunction

• Hyperacute rejection, often diagnosed intraoperatively on reperfusion of transplant
• Postischemic acute tubular necrosis causing delayed graft function
• Volume depletion
• Surgical complications:
  • Vascular thrombosis (either transplant renal artery or vein)
    • RAT: painless anuria and AKI, high risk of graft loss
  • Fluid collections (lymphocele, urinoma, perinephric hematoma)
  • Multiple renal arteries
• Atheroembolism
• Calcium oxalate deposits

Early and Late Dysfunction

• Acute rejection, usually within the first 12 months
  • Either cellular (usually after the first week) or antibody-mediated
• Calcineurin inhibitor nephrotoxicity, usually within the first three months
• Fluid collections (usually early)
  • Urinoma (within first few weeks)
  • Lymphocele (usually 2 to 6 weeks, but can be up to one year)
• Thrombotic microangiopathy
• Recurrent primary disease
• Transplant renal artery stenosis (usually late), caused by recurrent infections, rejection, or BK virus
• Urinary obstruction, from bladder or ureteric obstruction, which can result from fluid collections, urolithiasis, bladder dysfunction (especially in diabetes), or benign prostatic hypertrophy
• Viral infections, including BK virus and CMV, and, rarely, adenovirus
• New glomerular disease
  • Atypical HUS (>50%)
  • Membranoproliferative GN, including type 1 (20-50%) and type 2 (>50%)
  • Focal segmental glomerulosclerosis (20-40%)
  • IgA nephropathy (10-25%)
  • Membranous nephropathy (5-30%)
  • ANCA-associated GN (15-20%)
  • Lupus (5-30%)
  • Anti-GBM disease (<5%)
• Less commonly, retained ureteral stent and arteriovenous fistula after kidney allograft biopsy

Investigations

Acute Allograft Dysfunction

• Tacrolimus or cyclosporine levels
• BK level
• dd-cfDNA level
• US with Dopplers of renal artery and vein, looking for collections, thombosis, and patency of ureter

Management

Acute Allograft Dysfunction

• For patients >1 week post transplantation
• If fever, abdominal pain, or graft tenderness, assess for pyelonephritis
• If hypovolemic, increase oral fluid and follow creatinine
• If recent medication change, change it back and follow creatinine
• If CNI is supratherapeutic, decrease it and follow creatinine and CNI levels
• If above fails, check dd-cfDNA and BK viral load
  • If viral load of 10,000 copies/mL or greater, decrease immunosuppression and trend every 2 to 4 weeks
• If above fails, allograft biopsy is needed

Further Reading

• Acute and Chronic Allograft Dysfunction in Kidney Transplant Recipients. Medical Clin North America. 2016;100(3):487-503. doi: 10.1016/j.mcna.2016.01.002